Comprehensive Understanding of Interstitial Lung Disease in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is complicated in approximately 10% of RA patients. High titers of rheumatoid factor or anti-citrullinated protein antibodies (ACPAs), smoking, male gender, older age, longer disease duration, and higher articular disease activity are factors associated with the development of RA-ILD. Genetic factors such as human leukocyte antigen and peptidyl-arginine deiminase (PADI) and environmental factors such as smoking and periodontal disease could be associated with the activation of autoimmunity against citrullinated proteins, the synthesis of ACPAs, and the development of RA or RA-ILD. Metalloproteinase 7 and interferon-r-inducible protein 10 are serum novel biomarkers for the identification of RA-ILD, although surfactant protein A (SP-A), SP-D, and KL-6 are useful conventional biomarkers for the evaluation of RA-ILD. Novel antibodies against the PADI enzyme isoforms 3 and 4 or citrullinated heat shock protein (Hsp) 90a and Hsp90b are associated with RA-ILD and could be useful for predicting the development of RA-ILD. ILD is one of the main causes of mortality in RA. Therefore, prompt management of ILD in RA is necessary. To provide a better prognosis for RA-ILD patients, more efforts need to be made to determine the pathophysiology and the biomarkers for RA-ILD and the causal relationship between the development of ILD and DMARDs.